flavored clay-based therapeutic composition

ABSTRACT

The subject of the present invention is a flavored therapeutic composition containing a clay as well as active principle, and characterized in that the clay is a dioctahedral smectite and the flavor is encapsulated.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the U.S. National Stage filing of InternationalApplication No. PCT/FR2008/001185, filed Aug. 12, 2008, which claimspriority to EP 07291005.2, filed Aug. 13, 2007, the disclosures of whichare hereby incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

The present Application relates to a flavored pharmaceutical compositioncontaining a smectite as active ingredient.

A therapeutic composition based on smectite known as “diosmectite”exists and is sold under the trade-mark Smecta®. But due to theparticular taste of the clay which certain patients and children inparticular can sometimes find unpleasant, the problem was therefore tofind a novel composition which is flavored and the taste of whichremains predominant vis-à-vis the taste of the clay. In order to solvethis problem, the Applicant proposes a novel flavored pharmaceuticalcomposition based on smectite and as defined below.

DETAILED DESCRIPTION OF THE INVENTION

The subject of the present invention is therefore a flavored therapeuticcomposition containing a clay as active ingredient, and characterized inthat

-   -   the clay is a dioctahedral smectite; and    -   the flavored is encapsulated.

A composition according to the present invention can be used for theprevention and/or treatment of certain pathologies such as thesymptomatic treatment of pain associated with oesogastroduodenal andcolic conditions, acute and chronic diarrhoeas, coeliac disease.

Smectites represent a particular family of clay in which dioctaedralspecies such as montmorillonite and beidellite, and trioctaedral speciessuch as hectorite and saponite are found.

The clay used according to the invention is a dioctahedral smectite.Preferably, the dioctahedral smectite is a montmorillonite or abeidellite or a crystallographic structure intermediate between the twocrystal-chemical poles: montmorillonite and beidellite. Thisintermediate crystallographic structure can be close to themontmorillonite pole and even very close to the montmorillonite pole; itcan also be close to the beidellite pole and even very close to thebeidellite pole. Preferably, a smectite according to the invention is amontmorillonite or an intermediate structure close to themontmorillonite pole, and very preferably very close to themontmorillonite pole.

Also preferably, the clay used is the smectite known as “diosmectite”and sold under the trade-mark Smecta®.

The therapeutic composition according to the present invention comprises“a flavoring ingredient or composition”, called “flavor”. The term“flavor” as used in the present Application covers the flavoringingredients or compositions usually used in the food industry, whetherof natural or synthetic origin. It comprises single compounds ormixtures.

Specific examples of such compounds can be found in the literature, suchas for example in Fenaroli's Handbook of Flavor Ingredients, 1975, CRCPress; Synthetic Food Adjuncts, 1947, M. B. Jacobs, published by VanNostrand; or Perfume and Flavor Chemicals, 1969, S. Arctander,Montclair, N.J. (USA).

These compounds are well known to a person skilled in the art in thefield of flavoring or aromatizing consumer products, i.e. traditionallyflavored consumer products to which an odour, a flavor or a taste hasbeen added, or consumer products the taste of which has been modified.

Preferably, the flavor is a hydrophobic liquid, soluble in organicsolvents but only very weakly soluble in water.

Very preferably, the flavor is characterized by a Hildebrand solubilityparameter 8 less than 30 MPa^(1/2). The incompatibility with water ofmost of the flavors and perfumes can in fact be expressed by means ofthe Hildebrand solubility parameter which is in general less than 25MPa^(1/2) while the same parameter for water is 48 MPa^(1/2) and foralkanes, 15-16 MPa^(1/2). This parameter gives a useful polarity scalecorrelated with a cohesive energy density of the molecules. For mixingto take place spontaneously, the difference in solubility of themolecules to be mixed must be kept to a minimum. The handbook ofsolubility parameters (Handbook of Solubility Parameters, A. F. M.Barton, CRC Press, Bocca Raton, 1991) gives a list of 8 values for alarge number of chemical products but also recommendedgroup-contribution methods allowing the 8 values for complex chemicalstructures to be calculated.

Also preferably, the flavor is in a liquid, volatile or labile form,with a log P comprised within the range −2 to 7, and very preferably,from 2 to 6.

Also in a preferred fashion, a composition according to the presentinvention comprises, as flavor, natural extracts, essential oils or amixture thereof.

As a suitable flavor, traditional flavors can be mentioned such asliquorice, exotic fruits, red fruits, extracts of citrus fruits such aslime, lemon, orange, grapefruit, or mandarin oils or coffee, tea, mint,cocoa, vanilla/caramel or essential oils from herbs and spices, or alsoflavors known as “modern” such as coca-cola, green tea, caramel custard.

Preferably, a composition according to the invention comprises at leastone encapsulated flavor different from vanilla.

The flavors are preferably chosen from the traditional flavors such asliquorice, exotic fruits, red fruits, extracts of citrus fruits,vanilla/caramel/chocolate but also flavors known as “modern” suchcoca-cola, green tea, caramel custard.

Preferably, the flavor is chosen from vanilla/caramel/chocolate flavorsand extracts of citrus fruits and very preferably,vanilla/caramel/chocolate and orange, lemon, grapefruit or clementine.

Also in a preferred fashion, the flavor is a mixture of flavors, andvery preferably, a mixture of vanilla and orange flavors.

The flavor can be mixed with solvents, adjuvants, additives and/or othersubstances, for example those usually used in the flavor and/or foodindustry.

The flavor according to the present invention is preferably encapsulatedin a glassy matrix (encapsulation matrix) of carbohydrate(s).

Any sugar or sugar derivative which can be processed by extrusiontechniques can be used as constituent(s) of the encapsulation matrix, inorder to form a dry extruded solid. Particular examples of suitableconstituents can be chosen from the following products: sucrose,glucose, lactose, levulose, fructose, maltose, ribose, dextrose,isomalt, sorbitol, mannitol, xylitol, lactitol, maltitol, pentatol,arabinose, pentose, xylose, galactose, hydrogenated starch hydrolysates,maltodextrin, Stabilite (trade name; origin: SPI Polyols, USA), agar,carrageenan, other gums, polydextrose and the derivatives and mixturesthereof.

Preferably, maltodextrin or mixtures of maltodextrin and at least oneproduct chosen from: sucrose, glucose, lactose, levulose, maltose,fructose, isomalt, sorbitol, mannitol, xylitol, lactitol, maltitol andhydrogenated starch hydrolysates are used. Very preferably, the matrixis constituted by maltodextrin or a mixture of maltodextrin and at leastone product chosen from: sucrose, maltose, isomalt, maltitol andhydrogenated starch hydrolysates. Also very preferably, the matrix isconstituted by maltodextrin and sucrose.

Preferably, the maltodextrin has a dextrose equivalent (DE) greater than5 and less than 20.

An emulsifier such as lecithin, and/or a plasticizer, typically water,can be added to the mixture if necessary.

The flavored product or the flavored composition according to theinvention, which are extruded, can be prepared by any standard method.For example, the methods described in U.S. Pat. Nos. 4,610,890 and4,707,367, the content of which is incorporated by way of reference, aresuitable for supplying encapsulated flavors as used in the presentinvention.

Also preferably, the flavor is present in a proportion of at least 10%by weight expressed as dry matter, with respect to the total weight(expressed as dry matter) of the encapsulation matrix, and preferably ina proportion comprised between 15 and 35%.

A composition according to the invention comprises preferably 70 to 90%by weight of active ingredient, and very preferably from 75 to 85%, withrespect to the total weight of the composition.

Also preferably, a composition according to the invention comprises 0.1to 3% by weight of encapsulated flavor with respect to the total weightof the composition, and very preferably 0.3 to 2.5%. Also verypreferably, a composition according to the invention comprises 0.5 to 2%by weight of encapsulated flavour with respect to the total weight ofthe composition.

A therapeutic composition according to the present invention can bepresented in different solid forms such as for example powders,granules, tablets or capsules. Appropriate solid supports can be, forexample, talc, sugars, lactose, dextrin, gelatin, cellulose and itsesters.

In a therapeutic composition according to the present invention, therecan also be also other additives such as colouring agents, sweeteningagents, lubricants, glidants. A composition according to the presentinvention can also contain minerals.

The colouring agent(s) used according to the present invention can beany type of colouring agents usually used in the food and/or thepharmaceutical industries. Among the sweetening agents, the followingcan be mentioned: saccharin, aspartame, maltodextrin, monosaccharidessuch as fructose or glucose, disaccharides such as saccharose. Among thelubricating agents, talc can be mentioned for example. Among the glidantagents, saccharose can be mentioned.

The mineral contribution can for example consist of the addition ofmetal salts such as aluminium or magnesium salts such as aluminiumhydroxide, magnesium carbonate.

The administration method for a composition according to the inventionis chosen, among others, according to its pharmaceutical form and thepathology to be treated. Preferably, the composition as defined above isadministered by the oral route.

The daily administration dose is the usual recommended dose for thisproduct. In the particular case of the smectite known as “diosmectite”,it can be administered at a maximum daily dose of 18 g/day.

Unless defined otherwise, all the technical and scientific terms usedhere have the same meaning as that usually understood by an ordinaryspecialist in the field to which this invention belongs.

EXPERIMENTAL PART Example 1 Preparation of an Encapsulated Orange (Oil)Flavor

A syrup is prepared from maltodextrin, sucrose, water and flavor. Themixture is then heated to 123° C. in order to reduce the moisturecontent of the syrup. Then, the emulsifier is mixed with theconcentrated syrup under high shear conditions in order to form auniform melt. The melt is then extruded under a pressure of 2×10⁵ Pathrough an extrusion die plate with holes of 0.8 mm diameter in a coldsolvent for chilling and breaking of the extrudates.

Ingredients in grams (g) % dry matter Maltodextrin 18DE 1505 44.55Sucrose 1505 44.55 Cold-pressed oil of Valencia orange 350 10.36 Soyalecithin¹⁾ 18 0.54 Water 400 — Total 100.00 ¹⁾origin: Central Soya,Strong Wayne, Indiana, USA

Example 2 Preparation of an Encapsulated Vanilla Flavor

Example 1 is reproduced by using a vanilla extract (ex Firmenich)instead of the orange flavor.

Example 3 Preparation of an Encapsulated Caramel Flavor

Example 1 is reproduced by using a caramel flavor (ex Firmenich) insteadof the orange flavor.

Example 4 Preparation of a Flavored Therapeutic Composition

The compositions below are prepared by gently mixing all the substancestogether in the proportions indicated, until they are dispersed in ahomogenous fashion. In the table below, all the quantities are expressedin mg.

Example Example Example Ingredients 4a 4b 4c Diosmectite 3000 3000 3000Encapsulated orange flavor — — 10 (flavor prepared according toExample 1) ¹ Encapsulated vanilla flavor 50 50 50 (flavor preparedaccording to Example 2) ² Encapsulated caramel ® flavor 10 — — (flavorprepared according to Example 3) ³ Soluble saccharine + hydrated 700 710700 glucose Water 100 100 100 ¹ ex Firmenich, ref. 501289 TD 0990B; ² exFirmenich, ref. 501465 TD1591; ³ ex Firmenich, ref. 501403 TD 1094

Example 5 Stability of a Composition According to the Invention

Clay being a stable product naturally, the stability of a compositionaccording to the invention is measured both as regards the organolepticcharacteristics of the flavor and for its inertia vis-à-vis the clay.

The stability of the organoleptic characteristics of the flavor isestablished by testers (panel of 7 experts) on the basis of a number ofcriteria (sugary, fruity, acidic, bitterness, etc.) over a period of atleast 6 months.

Moreover, it is noted that the flavor shows no deterioration in thepresence of the clay over this same period.

1. A flavored therapeutic composition comprising a clay as an activeingredient, wherein the clay is a dioctahedral smectite; and the flavoris encapsulated.
 2. The composition according to claim 1, wherein thedioctahedral smectite is a montmorillonite or a beidellite or anintermediate crystallographic structure between montmorillonite andbeidellite crystal-chemical poles.
 3. The composition according to claim1, wherein the dioctahedral smectite is a montmorillonite or anintermediate crystallographic structure close to the montmorillonitepole.
 4. The composition according to claim 1, wherein the dioctahedralsmectite is a montmorillonite or an intermediate crystallographicstructure very close to the montmorillonite pole.
 5. The compositionaccording to claim 1, wherein the dioctahedral smectite is adiosmectite.
 6. The composition according to claim 1, wherein the flavoris a hydrophobic liquid.
 7. The composition according to claim 1,wherein the flavor has a Hildebrand solubility parameter less than 30MPa^(1/2).
 8. The composition according to claim 1, wherein the flavoris in liquid form with a log P comprised within the range −2 to
 7. 9.The composition according to claim 1, wherein the flavor has a log Pcomprised within the range 2 to
 6. 10. The composition according toclaim 1, wherein the flavor is a natural extract, an essential oil or amixture thereof.
 11. The composition according to claim 1, wherein thecomposition comprises at least one encapsulated flavor different fromvanilla.
 12. The composition according to claim 1, wherein the flavor isliquorice, exotic fruits, red fruits, extracts of citrus fruits,vanilla, caramel, chocolate, coca-cola, green tea, caramel custard, ormixtures thereof.
 13. The composition according to claim 1, wherein theflavor is vanilla, caramel, chocolate, extracts of citrus fruits, ormixtures thereof.
 14. The composition according to claim 1, wherein theflavor is vanilla, caramel, chocolate, orange, lemon, grapefruit,clementine, or mixtures thereof.
 15. The composition according to claim1, wherein the flavor is a mixture of flavors.
 16. The compositionaccording to claim 1, wherein the flavor is a mixture of vanilla andorange flavors.
 17. The composition according to claim 1, wherein theflavor is encapsulated in a glassy matrix of carbohydrates.
 18. Thecomposition according to claim 17, wherein the matrix comprisesmaltodextrin or a mixture of maltodextrin and at least one of sucrose,glucose, lactose, levulose, maltose, fructose, isomalt, sorbitol,mannitol, xylitol, lactitol, maltitol or hydrogenated starchhydrolysates.
 19. The composition according to claim 17, wherein thematrix comprises maltodextrin or a mixture of maltodextrin and at leastone of sucrose, maltose, isomalt, maltitol, or hydrogenated starchhydrolysate.
 20. The composition according to claim 17, wherein ene thematrix comprises maltodextrin and sucrose.
 21. The composition accordingto claim 18, wherein the maltodextrin has a dextrose equivalent greaterthan 5 and less than
 20. 22. The composition according to claim 1,wherein the flavor is present in a proportion of at least 10% by weightexpressed as dry matter, with respect to the total weight of theencapsulation matrix expressed as dry matter.
 23. The compositionaccording to claim 1, wherein the flavor is present in a proportioncomprised between 15 and 35% by weight expressed as dry matter, withrespect to the total weight of the encapsulation matrix expressed as drymatter.
 24. The composition according to claim 1, wherein thecomposition comprises from 70 to 90% by weight of active ingredient. 25.The composition according to claim 1, wherein the composition comprisesfrom 75 to 85% by weight of active ingredient.
 26. The compositionaccording to claim 1, wherein the composition comprises from 0.1 to 3%by weight of encapsulated flavor.
 27. The composition according to claim1, wherein the composition comprises from 0.3 to 2.5% by weight ofencapsulated flavor.
 28. The composition according to claim 1, whereinthe composition comprises from 0.5 to 2% by weight of encapsulatedflavor.